A major problem of cocaine addiction is the high risk of relapse even after years of abstinence. A drug-related environment can be enough to induce relapse. The mesolimbic dopamine (DA) system in the brain is known to be affected by most drugs of abuse. In particular, DA levels in specific regions of this system are related to reinforcement of cocaine use. However, little is known about the role of DA-related neuropeptides, such as neurotensin (NT) and dynorphin (Dyn), in mediating cocaine effects. The long-term goal of the proposed research project is to understand specific molecular aspects of cocaine addiction. Rats, as the animal model, will be trained to self-administer cocaine based on a cocaine-seeking behavior paradigm. Reinstatement of that behavior will be environmentally induced after a period of extinction. The specific aim is to characterize the role of NT and Dyn in the reinstatement of environmentally induced cocaine-seeking behavior. Understanding the effects of cocaine in these neurotransmitter systems and the roles of some of its components in environmentally-induced reinstatement of cocaine seeking behavior will provide new insights into the mechanisms of action of cocaine, the role of the environment in relapse, and will be very useful in the design of new and effective therapeutical approaches. [unreadable] [unreadable]